Strong antibody responses induced by protein antigens conjugated onto the surface of lecithin-based nanoparticles

J Control Release. 2010 Jan 4;141(1):93-100. doi: 10.1016/j.jconrel.2009.08.023. Epub 2009 Sep 1.

Abstract

An accumulation of research over the years has demonstrated the utility of nanoparticles as antigen carriers with adjuvant activity. Herein we defined the adjuvanticity of a novel lecithin-based nanoparticle engineered from emulsions. The nanoparticles were spheres of around 200nm. Model protein antigens, bovine serum albumin (BSA) or Bacillus anthracis protective antigen (PA) protein, were covalently conjugated onto the nanoparticles. Mice immunized with the BSA-conjugated nanoparticles developed strong anti-BSA antibody responses comparable to that induced by BSA adjuvanted with incomplete Freund's adjuvant and 6.5-fold stronger than that induced by BSA adsorbed onto aluminum hydroxide. Immunization of mice with the PA-conjugated nanoparticles elicited a quick, strong, and durable anti-PA antibody response that afforded protection of the mice against a lethal dose of anthrax lethal toxin challenge. The potent adjuvanticity of the nanoparticles was likely due to their ability to move the antigens into local draining lymph nodes, to enhance the uptake of the antigens by antigen-presenting cells (APCs), and to activate APCs. This novel nanoparticle system has the potential to serve as a universal protein-based vaccine carrier capable of inducing strong immune responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / drug effects*
  • Antibody Formation / immunology
  • Antigens, Bacterial / administration & dosage*
  • Antigens, Bacterial / immunology
  • Bacterial Toxins / administration & dosage*
  • Bacterial Toxins / immunology
  • Cell Line
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Drug Carriers / chemistry*
  • Drug Compounding
  • Drug Stability
  • Emulsions
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Immunization
  • Lecithins / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron, Transmission
  • Nanoparticles / chemistry*
  • Neutralization Tests
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / immunology
  • Serum Albumin, Bovine / administration & dosage*
  • Serum Albumin, Bovine / immunology
  • Surface Properties

Substances

  • Antigens, Bacterial
  • Bacterial Toxins
  • Drug Carriers
  • Emulsions
  • Lecithins
  • Recombinant Proteins
  • anthrax toxin
  • Serum Albumin, Bovine